Over 31 million Americans describe chronic sinusitis as a major health problem. Despite its high prevalence and the fact that millions of dollars are spent on treatment, there have been essentially no definitive studies of the etiology, pathogenesis, and therapy of this condition. Epithelial inflammation and hyperplasia are consistent and striking features of chronic sinusitis. In fact, epithelial thickening, imaged by CT and MRI scans, is the supporting diagnostic abnormality. The hypothesis is that environmental influences such as viruses, allergens and pollutions can act as precipitating factors in individuals with predispostion to sinusitis. These envrionmental factors induce epithelial alterations triggering inflammation and subsequently decrease mucociliary transport. Stasis of mucus in the sinuses facilitates bacterial infection, which may then further influence the epithelium. If this cycle is not disrupted, the epithelium develops metaplastic changes and the underlying mucosa proliferates, developing a self-perpetuating cycle that manifests clinically as chronic sinusitis which is no longer dependent on the bacteria or the anatomy. Thus, we hypothesize that, while alterations in epithelial function may be induced by several different mechanisms: it is the corruption of normal epithelial fundtion that is the final common pathway leading to the chronic manifestations of the diasease. In this study, we have developed a multidisciplinary approach to examine this hypothesis. Surgeons, pediatricians, pulmonologists and allergists have combined with basic scientists to focus their efforts on the role of the epithelium in 378 patients with the most persistent forms of chronic sinusitis. In particular, we wil examine four aspects: 1) inherent genetic defects in epithelial function, 2) viral infections as a precipitating factor in epithelial function, 3) functional alterations in epithelial ion transport and mucus secretion, and 4) the interaction of allergic and neurogenic inflammation in nasal and sinus mucosa in vivo. The interactions among invetsigators from diverse disciplines should provide novel information about pathogenesis and lead to new management strategies.